Naltrexone is a medication that has been used in the United States for the
treatment of alcoholism since its 1994 approval by the federal Food and Drug
Administration. Many of the original studies of naltrexone’s effectiveness,
however, examined alcohol-dependent patients with an “Anglo-Saxon”
or “Scandinavian drinking pattern,” that is, greater drinking on
holidays and weekends. Conversely, individuals with a “Mediterranean drinking
pattern” tend to regularly consume alcohol during the week, particularly
with meals. A study in the September issue of Alcoholism: Clinical &
Experimental Research is among the first to examine the effectiveness and
safety of naltrexone for the treatment of alcoholism among Spanish patients
with a Mediterranean drinking pattern.

“Years ago,” said José Guardia, a consultant at the Hospital
de la Santa Creu i Sant Pau in Barcelona, Spain and lead author of the study,
“there was a clear difference between drinking patterns in the northern
and southern countries of Europe. The Anglo-Saxon/Scandinavian tendency was
to drink more on holidays and weekends. In France, Italy, Spain and other Mediterranean
countries, wine was usually consumed with meals. However, when everyday consumption
becomes heavy, and after a long period of time, severe withdrawal and organic
consequences of chronic alcohol toxicity are probable. We wanted to see if there
would be differences in using naltrexone for the treatment of alcohol dependency
in this population.”

Drugs can have agonist and/or antagonist properties. Agonists activate a receptor
to achieve their effect. Antagonists block the receptor from being activated
by an endogenous (produced within the organism) or exogenous (produced outside
the organism) chemical. Naltrexone acts as an opioid antagonist within the opioid
neurotransmitter system, which is a part of the brain’s reward system.
When opioids are stimulated, levels of the dopamine neurotransmitter are increased,
leading to the “high” that is associated with a variety of drugs.
Naltrexone “blocks” the opioid receptor from being activated. It
was first developed in the 1970s to block heroin from activating the receptors
for opiates, later becoming approved for the treatment of heroin addiction in
the mid-1980s. In the late 1980s, researchers began to suspect it might have
uses for the treatment of alcohol addiction.

For the Guardia study, subjects were 202 alcohol-dependent patients (151 males,
51 females), 18 to 60 years of age, who were seeking outpatient treatment from
seven different treatment centers in Spain. Patients were randomly assigned
to 12 weeks of treatment with either 50 mg/day of naltrexone (n=101) or an identical-looking
placebo (n=101). Patient treatment also included a “psycho-social intervention,”
consisting of a weekly session of supportive group therapy, a weekly visit with
the study physician, and a nurse intervention three times a week. Following
treatment, researchers evaluated the relapse rate, alcohol- consumption levels,
craving, adverse effects, changes in the biochemical markers of heavy drinking,
and possible toxicity among the final tally of 192 patients considered eligible
for evaluation.

Of the naltrexone-treated subjects, only 7.9 percent (n=8) relapsed to heavy
drinking. (Heavy drinking was defined as more than five drinks per day for men,
more than four drinks per day for women, or more than five drinking days per
week for both genders.) Of the placebo-treated subjects, 18.8 percent (n=19)
relapsed to heavy drinking. The adverse effects known to be associated with
naltrexone use (nausea, headache, abdominal discomfort, sleepiness) were low
among those treated, confirming previous studies of naltrexone’s safety
and tolerability.

“The most significant finding of our study was that naltrexone-treated
alcohol-dependent subjects showed a reduced relapse rate to heavy drinking,”
said Guardia, “in comparison with those patients treated with a placebo.
These results demonstrate the synergistic effects of combining pharmacotherapy
with psycho-social intervention. We know that alcoholism is a recoverable disease.
These results show that when alcohol-dependent patients get the appropriate
psycho-social intervention plus pharmacotherapy for a suitable amount of time,
they can overcome this addictive disease.”

“These results open up the possibility for European alcohol-dependent
patients to receive treatment with naltrexone,” said José Pérez
de los Cobos, a psychiatrist with the Addictive Behavior Unit at the Hospital
de la Santa Creu i Sant Pau. In fact, since this study was conducted, naltrexone
has been authorized for the treatment of alcoholism in Spain. “Furthermore,”
he added, “once we understand the effectiveness of naltrexone, we can
go on to explore its limitations. That way, future research can examine how
combining naltrexone with other medications, and even more effective psycho-social
interventions, can treat alcoholism.”

Funding for this Addiction Science Made Easy project is provided by the Addiction Technology Transfer Center National Office, under the cooperative agreement from the Center for Substance Abuse Treatment of SAMHSA.